Linkage to chromosome 4p16.3 has been found in an extended family from Tennessee with autosomal dominant, low frequency, progressive sensorineural hearing loss. This is the same region that contains IT15, the gene causing Huntington's disease. This region of the genome is relatively well mapped because of the interest in IT15. Analysis of recombinant individual maps the disease gene to a genomic region of about 500,000 base pairs between D4S412 and D4S1071. A mouse model, titled (tlt) is mapped to the syntenic region of human 4p16.3 on mouse chromosome 5. There is only one gene currently mapped to this segment. Additional studies will yield the gene responsible for nonsyndromic hearing loss in this family. One consanguineous family from Ichalkaranji, India, with recessive nonsyndromic hearing impairment has been mapped. The LOD score for this family is greater than 3. Additional work should not only raise the LOD score, but also determine how many additional families from India are linked to this same locus. Efforts at improving subtraction techniques for cDNA libraries have resulted in an enhancement over previous attempts. The levels of actin, a ubiquitously expressed abundant in RNA, were lowered by more than 98%. The levels of transferrin receptor, a ubiquitous message that is considered to be rare in all tissues, were lowered by 93%. Several clones were analyzed and found to be greatly enriched in the organ of Corti when compared with the brain.